Recent evidence from 2 large clinical trails has firmly established the benefit of carotid endarterectomy (CE) for patients with symptomatic high grade carotid stenosis. Trials currently underway will further define the role of this surgical procedure for asymptomatic patients and for those with more moderate carotid stenosis. The increased scientific investigation of CE, and discovery of a reduction in fatal and non-fatal stroke following the procedure, has led to an increase in the use of CE. This is likely to continue. Although CE produces long term benefits, there is also a substantial immediate perioperative risk of stroke and death. Consequently, it is crucial that we investigate means of reducing this risk. An uncontrolled observation from the NASCET trial suggests that it may be possible to reduce the perioperative risk of CE through a simple regimen consisting of a daily dose of 650 to 1300 mg of ASA started prior to surgery. Although the value of ASA in stroke prevention has been clearly established over the last decade, disagreement exists over the appropriate dose for primary prevention and no useful information exists on dosage effects in patients undergoing surgery to the carotid artery. In the proposed trial, patients scheduled for carotid endarterectomy at centers currently participating in the NASCET collaborative study group, will be randomly assigned, before surgery, to one of 4 drug regimens consisting of ASA at a daily dose of 80 mg, 325 mg, 650 mg, or 1300 mg, to be continued for 90 days. These patients will be followed for 3 months from surgery to record all strokes, deaths and changes in functional status. These outcomes will form the basis for the comparison of the 4 ASA dosage groups. Approximately 100,000 individuals undergo CE in the U.S.A. and Canada each year. Currently about 6%, or 6000, of these patients suffer stroke or death within 30 days of surgery. A 50% reduction in this event rate would thus spare 3000 individuals from stroke and death each year, and would give increased confidence to both those offering and those receiving this surgical procedure. The proposed trial will determine whether such benefits exist and provide the information needed to estimate the magnitude of risk reduction that might be achievable with a simple ASA treatment regimen.